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2012 Fiscal Year Final Research Report

Cellular and animal models for intracellular TDP-43 aggregates

Research Project

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Project/Area Number 22500345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research Institution公益財団法人東京都医学総合研究所 (2012)
Tokyo Metropolitan Organization for Medical Research (2010-2011)

Principal Investigator

NONAKA Takashi  公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 副参事研究員 (30356258)

Project Period (FY) 2010 – 2012
Keywords筋萎縮性側索硬化症 / TDP-43
Research Abstract

We established a new cellular model for intracellular TDP-43 aggregate formation and screened small molecules which inhibit the formation of TDP-43 aggregates using this model. These compounds may be possible new drugs for the treatment of ALS and FTLD-TDP.

  • Research Products

    (43 results)

All 2013 2012 2011 2010

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (23 results) Patent(Industrial Property Rights) (7 results)

  • [Journal Article] Methylene Blue Reduced Abnormal Tau Accumulation in P301L Tau Transgenic Mice2012

    • Author(s)
      Masato Hosokawa, Tetsuaki Arai, Masami Masuda-Suzukake, Takashi Nonaka, Makiko Yamashita, Haruhiko Akiyama, Masato Hasegawa
    • Journal Title

      PLoS ONE

      Pages: e52389

    • Peer Reviewed
  • [Journal Article] Molecular analysis and biochemical classification of TDP-43 proteinopathy2012

    • Author(s)
      Tsuji H, Arai T, Kametani F, Nonaka T, Yamashita M, Suzukake M, Hosokawa M, Yoshida M, Hatsuta H, Takao M, Saito Y, Murayama S, Akiyama H, Hasegawa M, Mann DM, Tamaoka A
    • Journal Title

      Brain

      Volume: 135 Pages: 3380-3391

    • Peer Reviewed
  • [Journal Article] Inhibition of TDP-43 Accumulation by Bis(thiosemicarbazonato)-Copper Complexes2012

    • Author(s)
      Parker SJ, Meyerowitz J, James JL, Liddell JR, Nonaka T, Hasegawa M, Kanninen KM, Lim S, Paterson BM, Donnelly PS, Crouch PJ, White AR
    • Journal Title

      PLoS One

      Volume: 7(8) Pages: e42277

    • Peer Reviewed
  • [Journal Article] Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells2012

    • Author(s)
      Egawa N, Kitaoka S, Tsukita K, Naitoh M, Takahashi K, Yamamoto T, Adachi F, Kondo T, Okita K, Asaka I, Aoi T, Watanabe A, Yamada Y, Morizane A, Takahashi J, Ayaki T, Ito H, Yoshikawa K, Yamawaki S, Suzuki S, Watanabe D, Hioki H, Kaneko T, Makioka K, Okamoto K, Takuma H, Tamaoka A, Hasegawa K, Nonaka T, Hasegawa M, Kawata A, Yoshida M, Nakahata T, Takahashi R, Marchetto MC, Gage FH, Yamanaka S, Inoue H
    • Journal Title

      Sci. Transl. Med

      Volume: 4(145) Pages: 145ra104

    • Peer Reviewed
  • [Journal Article] Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells2012

    • Author(s)
      Takahashi M, Tin Y, Nonaka T, Hasegawa M, Watanabe N, and Arai T
    • Journal Title

      Neurosci. Lett

      Volume: 510 Pages: 48-52

    • Peer Reviewed
  • [Journal Article] Epitope mapping of antibodies against TDP-43 and detection of protease-resistant fragments of pathological TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration2012

    • Author(s)
      Tsuji H, Nonaka T, Yamashita M, Suzukake M, Kametani F, Akiyama H, Mann DM, Tamaoka A, Hasegawa M
    • Journal Title

      Biochem. Biophys. Res. Comm

      Volume: 417 Pages: 116-121

    • Peer Reviewed
  • [Journal Article] C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress2011

    • Author(s)
      Meyerowitz J, Parker SJ, Vella LJ, Ng DC, Price KA, Liddell JR, Caragounis A, Li QX, Masters CL, Nonaka T, Hasegawa M, Bogoyevitch MA, Kanninen KM, Crouch PJ, White AR
    • Journal Title

      Mol. Neurodegener

      Volume: 6 Pages: 57

    • Peer Reviewed
  • [Journal Article] Molecular Dissection of TDP-43 Proteinopathies2011

    • Author(s)
      Hasegawa M, Nonaka T, Tsuji H, Tamaoka A, Yamashita M, Kametani F, Yoshida M, Arai T, Akiyama H
    • Journal Title

      J Mol Neurosci

      Volume: 45 Pages: 480-485

    • Peer Reviewed
  • [Journal Article] In vitro recapitulation of aberrant protein inclusions in neurodegenerative diseases: New cellular models of neurodegenerative diseases2011

    • Author(s)
      Nonaka T* and Hasegawa M*
    • Journal Title

      Communicative & Integrative Biology

      Volume: 4 Pages: 501-502

    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of the hypocretin/orexin gene by NR6A12010

    • Author(s)
      Tanaka S, Kodama T, Nonaka T, Toyoda H, Arai M, Fukazawa M, Honda Y, Honda M, Mignot E
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 403 Pages: 178-183

    • Peer Reviewed
  • [Journal Article] Seeded aggregation and toxicity of alpha-synuclein and tau: cellular models of neurodegenerative diseases2010

    • Author(s)
      Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M
    • Journal Title

      J. Biol. Chem

      Volume: 285 Pages: 34885-34898

    • Peer Reviewed
  • [Journal Article] Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathy2010

    • Author(s)
      Arai T, Hasegawa M, Nonaka T, Kametani F, Yamashita M, Hosokawa M, Niizato K, Tsuchiya K, Kobayashi Z, Ikeda K, Yoshida M, Onaya M, Fujishiro H and Akiyama H
    • Journal Title

      Neuropathol

      Volume: 30 Pages: 372-380

    • Peer Reviewed
  • [Journal Article] Characterization of Inhibitor-Bound alpha-Synuclein Dimer: Role of alpha-Synuclein N-Terminal Region in Dimerization and Inhibitor Binding2010

    • Author(s)
      Yamaguchi Y, Masuda M, Sasakawa H, Nonaka T, Hanashima S, Hisanaga S, Kato K, Hasegawa M
    • Journal Title

      J. Mol. Biol

      Volume: 395 Pages: 445-456

    • Peer Reviewed
  • [Presentation] Intracellular seeding model reproduces characteristic features of affected neurons in TDP-43 proteinopathy2012

    • Author(s)
      Takashi Nonaka, Masami Masuda-Suzukake, Yoko Hasegawa,Mari Yoshida, Shigeo Murayama,David Mann, Haruhiko Akiyama and Masato Hasegawa
    • Organizer
      The 8th International Conference on Fronttemporal Dementias
    • Place of Presentation
      Manchester, UK
    • Year and Date
      20120905-07
  • [Presentation] 患者脳に蓄積したTDP-43のプリオン様性質2012

    • Author(s)
      野中隆,鈴掛(増田)雅美,新井哲明,吉田眞理,村山繁雄,Mann David,秋山治彦,長谷川成人
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-15
  • [Presentation] シード依存的な細胞内TDP-43蓄積による細胞死の誘導2012

    • Author(s)
      野中隆,鈴掛(増田)雅美,新井哲明,吉田眞理,村山繁雄,Mann David,秋山治彦,長谷川成人
    • Organizer
      第31回日本認知症学会学術集会
    • Place of Presentation
      筑波
    • Year and Date
      2012-10-27
  • [Presentation] Intracellular seeded aggregation and cytotoxic model of TDP-432012

    • Author(s)
      Takashi Nonaka, Masami Masuda-Suzukake, Makiko Yamashita, Masato Hosokawa, Haruhiko Akiyama and Masato Hasegawa
    • Organizer
      Alzheimer's Association International Conference (AAIC)2012
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2012-07-16
  • [Presentation] TDP-43のシード依存的細胞内凝集体形成2012

    • Author(s)
      野中隆、長谷川成人
    • Organizer
      第53回日本神経学会学術大会、シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-05-24
  • [Presentation] メチレンブルーによるリン酸化タウ蓄積抑制効果の検討2012

    • Author(s)
      細川雅人,新井哲明,野中隆,山下万貴子,鈴掛雅美,辻浩史,長谷川成人,秋山治彦
    • Organizer
      第132回 日本薬学会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-29
  • [Presentation] Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells2011

    • Author(s)
      Muneaki Takahashi, Takashi Nonaka, Masato Hasegawa, Nobuo Watanabe, Takao Arai
    • Organizer
      SOCIETY FOR FREE RADICAL BIOLOGY AND MEDICINE SFRBM's 18th Annual Meeting
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      20111116-20
  • [Presentation] Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells2011

    • Author(s)
      Muneaki Takahashi, Takashi Nonaka, Masato Hasegawa, Nobuo Watanabea, Takao Araia
    • Organizer
      5th Biennial Meeting of Society for Free Radical Research-Asia (SFRR-Asia) 2011
    • Place of Presentation
      Kagoshima, Japan
    • Year and Date
      20110831-0904
  • [Presentation] Progranulin reduction affects tau phosphorylation in P301L tau transgenic mice2011

    • Author(s)
      M. HOSOKAWA; T. ARAI; T. NONAKA; M. YAMASHITA; M. SUZUKAKE; T. MATSUWAKI; M. NISHIHARA; M. HASEGAWA; H. AKIYAMA
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-13
  • [Presentation] Heat shock protein 90 (HSP90) suppresses cell death induced by cytoplasmic TDP-43 and inositol hexakisphosphate kinase 22011

    • Author(s)
      E. NAGATA; T. NONAKA; Y. MORIYA; A. SAIARDI; Y. OKADA; H. TSUKAMOTO; J. ITOH; T. SATOH; T. ARAI; S. TAKIZAWA; F. YOSHII; M. HASEGAWA; S. TAKAGI
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-13
  • [Presentation] FTLD-TDPおよびALSに蓄積するTDP-43蛋白の凝集体構造に関する解析2011

    • Author(s)
      辻浩史、野中隆、新井哲明、山下万喜子、亀谷富由樹、細川雅人、初田裕幸、高尾昌樹、村山繁雄、斉藤祐子、長谷川成人、秋山治彦、David Mann、詫間浩、玉岡晃
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-12
  • [Presentation] 細胞内異常蛋白質の伝播の可能性2011

    • Author(s)
      長谷川成人、野中隆、辻浩史、山下万喜子、増田雅美、玉岡晃、Mann David,村山繁雄、新井哲明、秋山治彦
    • Organizer
      第30回日本認知症学会学術集会、シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
  • [Presentation] メチレンブルーによるリン酸化タウ蓄積抑制効果の検討2011

    • Author(s)
      細川雅人、新井哲明、野中隆、山下万喜子、鈴掛雅美、辻浩史、長谷川成人、秋山治彦
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
  • [Presentation] FTDP-17が疑われた日本人患者75症例におけるPGRNとMAPT 遺伝子解析2011

    • Author(s)
      大垣光太郎、李元哲、高梨雅史、石川景一、小林智則、中西淳、野中隆、長谷川成人、岸 雅彦、吉野浩代、舩山学、塩屋敬一、横地正之、佐々木良元、小久保康昌、葛原茂樹、本井ゆみ子、富山弘幸、服部信孝
    • Organizer
      第5回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京
    • Year and Date
      2011-10-07
  • [Presentation] Cellular models of seeded aggregation of alpha-synuclein and tau2011

    • Author(s)
      Takashi Nonaka, Sayuri T. Watanabe, Takeshi Iwatsubo, Masato Hasegawa
    • Organizer
      International conference on Alzheimer's disease and related disorders (ICAD) 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-17
  • [Presentation] Histopathological Analysis of Progranulin Knockout Mice2011

    • Author(s)
      Tetsuaki Arai, Katsuyoshi Mizukami, Masugi Nishihara, Masato Hosokawa, Takashi Nonaka, Masato Hasegawa, Haruhiko Akiyama, Takashi Matsuwaki, Sho Takahashi, Takashi Asada
    • Organizer
      International conference on Alzheimer's disease and related disorders (ICAD) 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-17
  • [Presentation] C-terminal TDP-43 Inclusion Suppress Proliferation Mediated by Transcriptional Dysregulation2011

    • Author(s)
      Makiko Yamashita, Takashi Nonaka, Masato Hasegawa, Haruhiko Akiyama
    • Organizer
      International conference on Alzheimer's disease and related disorders (ICAD) 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-17
  • [Presentation] Quantitative Determination of TDP-43 in Cerebrospinal Fluid of Patients With Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disorders2011

    • Author(s)
      Masato Hosokawa, Haruhiko Akiyama, Tetsuaki Arai, Hiroshi Tsuji, Takashi Nonaka, Makiko Yamashita, Masato Hasegawa
    • Organizer
      International conference on Alzheimer's disease and related disorders (ICAD) 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-17
  • [Presentation] TDP-43による運動ニューロン変性の分子病態2011

    • Author(s)
      野中隆、長谷川成人
    • Organizer
      第52回日本神経学会学術大会、シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
  • [Presentation] 神経変性疾患における蛋白癌仮説2011

    • Author(s)
      長谷川成人、野中隆、辻浩史、山下万喜子、増田雅美、玉岡晃、村山繁雄、新井哲明、秋山治彦
    • Organizer
      第52回日本神経学会学術大会、シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
  • [Presentation] ALSおよびFTLD-TDPに蓄積するリン酸化TDP-43蛋白コンフォメーションに関する解析2011

    • Author(s)
      辻浩史、長谷川成人、野中隆、亀谷富由樹、山下万喜子、増田雅美、細川雅人、秋山治彦、David Mann、初田裕幸、高尾昌樹、村山繁雄、斉藤祐子、詫間浩、冨所康志、中馬越清隆、石井亜紀子、石井一弘、渡邉雅彦、新井哲明、玉岡晃
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
  • [Presentation] 細胞質内TDP-43凝集体形成細胞でのイノシトール6リン酸キナーゼ2の役割2011

    • Author(s)
      永田栄一郎、野中隆、森谷祐介、岡田義則、佐藤忠之、塚本秀雄、新井哲明、長谷川成人、瀧澤俊也、高木繁治
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
  • [Presentation] FTDP-17が疑われた日本人75症例におけるPGRNとMAPT遺伝子解析2011

    • Author(s)
      大垣光太郎、李元哲、高梨雅史、石川景一、小林智則、中西淳、野中隆、長谷川成人、岸雅彦、吉野浩代、舩山学、塩谷敬一、横地正之、佐々木良元、小久保康昌、葛原茂樹、本井ゆみ子、富山弘幸、服部信孝
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-18
  • [Patent(Industrial Property Rights)] フルベストラントを含む神経変性疾患の治療又は予防のための医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 72977
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] アモジアキンを含む神経変性疾患の治療又は予防のための医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 72983
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] ミトタンを含む神経変性疾患の治療又は予防のための医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 72989
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] レチノイン酸等を含む神経変性疾患の治療及び/又は予防用医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 74114
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] ブロムヘキシン塩酸塩等を含む神経変性疾患の治療及び/又は予防用医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 74155
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] ニフェジピン等を含む神経変性疾患の治療及び/又は予防用医薬組成物2013

    • Inventor(s)
      山下 万貴子; 長谷川 成人; 秋山 治彦; 野中 隆
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、2013- 74065
    • Filing Date
      2013-03-29
  • [Patent(Industrial Property Rights)] 神経変性疾患治療用物質のスクリーニング方法2012

    • Inventor(s)
      野中 隆,長谷川成人,増田雅美
    • Industrial Property Rights Holder
      財団法人東京都医学総合研究所
    • Industrial Property Number
      特許、特許第4948845号
    • Acquisition Date
      2012-03-16

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Published: 2014-08-29  

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